Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2-related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families.
Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2-related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families.
复制标题
黑色素瘤细胞系和黑色素瘤家族中位于 1P36 的 P34CDC2 相关 CDC2L1 基因推定启动子区域的突变分析和多个多态性的鉴定。
DOI：
10.1002/ijc.10422
复制
发表时间：
2002
影响因子：
6.4
通讯作者：
Nelson,MarkA
中科院分区：
文献类型：
--
作者：
Feng,Yongmei;Shi,Jiaqi;Goldstein,AlisaM;Tucker,MargaretA;Nelson,MarkA
1号染色体异常是包括恶性黑色素瘤在内的许多癌症中最常检测到的畸变。在黑色素瘤中观察到的染色体1 p36区域的部分缺失和等位基因丢失表明在该区域存在推定的肿瘤抑制基因。一个候选基因，CDC 2L 1，编码PITSLRE蛋白相关的p34 cdc 2，定位于1 p36。为了确定CDC 2L 1突变是否参与黑色素瘤的发展，我们检查了20个黑色素瘤细胞系和11个与染色体1 p36相关的黑色素瘤易感家族成员。在20个黑色素瘤细胞系和6个黑色素瘤病例中，仅在UACC 903细胞系中发现1个突变（外显子7第97位C→T，Ser→Leu）。然而，在CDC 2L 1的推定启动子区域中鉴定出4个多态性核苷酸变化，C-48 T，G-53 C，T-103 C和T-210 C。这4个突变体均位于转录因子TCF 11、MZF 1和TAAC box的保守结合位点内或旁，可能对CDC 2L 1的表达具有调控作用。亚硫酸氢钠基因组测序未发现CDC 2L 1启动子区CpG岛异常甲基化。这些结果表明，突变是罕见的，在这些黑色素瘤细胞系和黑色素瘤家族中的CDC 2L 1基因和异常的胞嘧啶甲基化的CDC 2L 1 CpG岛是不是在黑色素瘤中的CDC 2L 1抑制的机制。4个启动子多态性对该基因转录调控的贡献及其与黑色素瘤的关系值得进一步研究。© 2002 Wiley利斯公司
Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanoma. Partial deletions and an allelic loss of the chromosome 1p36 region observed in melanoma indicate the presence of putative tumor suppressor gene(s) in this region. A candidate gene,CDC2L1, which encodes PITSLRE proteins related to p34cdc2, is mapped to 1p36. To determine whetherCDC2L1mutation is involved in melanoma development, we examined 20 melanoma cell lines and 11 members of melanoma‐prone families linked to chromosome 1p36. Mutation analysis throughout the entire coding region of theCDC2L1gene revealed only 1 mutation (C→T at nucleotide location 97 of exon 7, Ser→Leu) in the melanoma cell line UACC 903 out of 20 melanoma cell lines and 6 melanoma cases. However, 4 polymorphic nucleotide changes, C‐48T, G‐53C, T‐103C and T‐210C, in the putative promoter region ofCDC2L1were identified. The 4 variants were located within or beside the conserved binding sites of transcription factors TCF11, MZF1 and TAAC box, indicating their potential effects on the regulation ofCDC2L1expression. No aberrant methylation of theCDC2L1CpG island in the promoter region was observed by sodium bisulfite genomic sequencing. These results indicate that mutations are rare in theCDC2L1gene in these melanoma cell lines and melanoma families and that the aberrant cytosine methylation of theCDC2L1CpG island is not the mechanism ofCDC2L1repression in melanoma. The contribution of 4 promoter polymorphisms to the transcriptional regulation of the gene and its association with melanoma warrants further investigation. © 2002 Wiley‐Liss, Inc.